This project concerns basic research on the electromechanics of the cochlea, and its applications to cochlear pathology. The research on normal and modified cochleas is intertwined in such a way that cochlear modifications by noise exposure or pharmacological agents become tools in the analysis of the normal function by perturbation of its characteristics and, at the same time, the perturbed characteristics become symptomatic of specific pathologies. During the current project period emphasis has been on the role of the tectorial membrane in cochlear micromechanics. This work is being successfully concluded. The planned cochlear research focuses on two areas: 1) the cochlear active process (cochlear amplifier) and 2) the coding of frequency and intensity information. It is assumed that the active process is involved in an electromechanical feedback provided by the outer hair cells and that it is vulnerable to noise exposure and various pharmacological agents. By perturbing its function, we will attempt to isolate it from the other cochlear processes. Preliminary experiments performed in both areas have already provided new information. Injection of sodium salicylate into scala tympani altered the response phase of the outer hair cells. The receptor potentials of the cells recorded as functions of sound frequency showed that the frequency of maximum response changes strongly with sound intensity and, therefore, the maximum cannot constitute an adequate pitch code. The latter finding is relevant for cochlear prosthetics. The cochlear function is studied through intracellular recording from the outer and inner hair cells and from the supporting cells. A method developed on the project enables us to obtain a continuous magnitude or phase transfer function (magnitude or phase versus sound frequency) in 5 sec, so that a family of transfer functions can be obtained with sound intensity as a parameter within a time span compatible with our ability to hold a hair cell. From a family of the transfer functions it is possible to derive input-output functions (magnitude versus sound intensity) at an arbitrary number of sound frequencies and tuning curves for comparison with a large quantity of data in the literature. In addition to physiological work, morphological work will be performed to ascertain morphological changes associated with functional changes. This work will be performed with the help of serial sections of the organ of Corti for both light and electron microscopy. It will include in-vitro studies of hair-cell motility.